Potassium Carbonate → HCID 86708705, compound

HRID 1751330Notes

Reaction equation

HRID 1751330 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[CH:8]=[C:7]([C:12]1[NH:16][C:15]([C@@H:17]3[CH2:21][C@H:20]([OH:22])[CH2:19][N:18]3[C:23](=[O:33])[C@@H:24]([NH:28][C:29](=[O:32])[O:30][CH3:31])[CH:25]([CH3:27])[CH3:26])=[N:14][CH:13]=1)[CH:6]=[CH:5]2.CC1(C)C(C)(C)OB([C:42]2[CH:47]=[CH:46][C:45]([C:48]3[NH:52][C:51]([C@@H:53]4[CH2:57][CH2:56][CH2:55][N:54]4[C:58]([O:60][C:61]([CH3:64])([CH3:63])[CH3:62])=[O:59])=[N:50][CH:49]=3)=[CH:44][CH:43]=2)O1.C([O-])([O-])=O.[K+].[K+]>COCCOC.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[OH:22][C@@H:20]1[CH2:19][N:18]([C:23](=[O:33])[C@@H:24]([NH:28][C:29]([O:30][CH3:31])=[O:32])[CH:25]([CH3:26])[CH3:27])[C@H:17]([C:15]2[NH:16][C:12]([C:7]3[CH:8]=[C:9]4[C:4](=[CH:5][CH:6]=3)[CH:3]=[C:2]([C:42]3[CH:43]=[CH:44][C:45]([C:48]5[NH:52][C:51]([C@@H:53]6[CH2:57][CH2:56][CH2:55][N:54]6[C:58]([O:60][C:61]([CH3:64])([CH3:63])[CH3:62])=[O:59])=[N:50][CH:49]=5)=[CH:46][CH:47]=3)[CH:11]=[CH:10]4)=[CH:13][N:14]=2)[CH2:21]1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 56605289(s)-tert-Butyl 2-(5-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-1h-imidazol-2-yl)pyrrolidine-1-carboxylateHCID 86708706methyl (S)-1-((2S,4S)-2-(5-(6-bromonaphthalen-2-yl)-1H-imidazol-2-yl)-4-hydroxypyrrolidin-1-yl)-3-methyl-1-oxobutan-2-ylcarbamate

Product 1

HCID 86708705HCID 86708705, compoundYield 42.9%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
85 °C

Procedure

To a solution of methyl (S)-1-((2S,4S)-2-(5-(6-bromonaphthalen-2-yl)-1H-imidazol-2-yl)-4-hydroxypyrrolidin-1-yl)-3-methyl-1-oxobutan-2-ylcarbamate (100 mg, 0.19 mmol) in DME (2 mL) was added (S)-tert-butyl 2-(5-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-1H-imidazol-2-yl)pyrrolidine-1-carboxylate (83 mg, 0.19 mmol), Pd(PPh3)4 (22 mg, 0.019 mmol), and K2CO3 (2M in H2O, 0.32 mL, 0.63 mmol). The solution was degassed with N2 for 10 min, then heated to 85° C. for 18 h. The mixture was cooled to rt, diluted with EtOAc, and washed with sat. NaHCO3, brine, dried over MgSO4, and concentrated. The residue was purified by silica gel chromatography to yield product (61 mg).

Workup

  1. customThe solution was degassed with N2 for 10 min
  2. temperatureThe mixture was cooled to rt
  3. additiondiluted with EtOAc
  4. washwashed with sat. NaHCO3, brine
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated
  7. customThe residue was purified by silica gel chromatography

Sources & evidence

ORD record
ord-9ade54a0e29d42dfb0845437dddd24f3
Source dataset
uspto-grants-2015_10
Patent number
US09156823B2

Reaction notes

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